Background: Antifungal therapeutic drug monitoring (TDM) is critical for individualized, precision treatment and prevention of fungal infections, but previous research has highlighted low TDM utilization rates, potentially reflecting long turnaround times, complex testing logistics, results interpretation, and cost. Objectives: To inform strategies to increase antifungal TDM use, we assessed TDM-related knowledge, attitudes, and practices among infectious disease (ID) physicians and pharmacists. Methods: We summarized findings from three structured focus group discussions (FGD)—two with six ID physicians each and one with six pharmacists—during March 2024. Open-ended discussions were held regarding awareness of and experiences with fungal infections and TDM, perceptions of antifungal TDM such as potential benefits, barriers, and challenges to conducting antifungal TDM, and information needs about antifungal TDM. We conducted qualitative transcription-based analysis to identify themes. Results: Six themes emerged from FGDs: (1) variable knowledge and experience with antifungal TDM among participants, (2) the importance of close collaboration between physicians and pharmacists during the TDM process, (3) the main motivators driving TDM use were improving treatment outcomes, preventing toxicity, and addressing pharmacokinetic variability, (4) the perception that antifungal resistance was unrelated to TDM, (5) key barriers were a lack of comprehensive clinical guidelines, long lab testing turnaround times, complex testing logistics, and high costs, and (6) a need for additional clinical data on TDM's impact on outcomes. Conclusions: Our findings can inform efforts to increase TDM use by addressing barriers to practice. Development of evidence-based clinical guidelines and improvements in testing infrastructure across practice settings could increase antifungal TDM use. Published 2025. This article is a U.S. Government work and is in the public domain in the USA.

PURPOSE: Research has shown that the prevalence of vision difficulty is higher among US adults with low income than among those with higher income. We aimed to examine the trends in income-related inequalities in vision difficulty and to identify the contributions of explanatory factors. DESIGN: A cross-sectional and trend study. METHODS: Our study estimated income-related inequalities in self-reported vision difficulty among US adults aged 18 years or older using data from the National Health Interview Survey (NHIS) during 1999-2018. The concentration index was used to measure income-related inequality in vision difficulty and was decomposed into contributing factors. We examined temporal changes in income-related vision difficulty inequalities and contributors to those changes from 1999 to 2018. RESULTS: We found that vision difficulty was concentrated among lower income groups and the degree of income-related inequality in vision difficulty widened between 1999 and 2018. Decomposition analysis revealed that poverty-to-income ratio and public health insurance coverage were important contributors to income-related inequalities in vision difficulty, with smaller contributions made by smoking, physical inactivity, and female sex. Among all variables, non-White race/ethnicity, lower physical activity, and poverty-to-income ratio were important factors explaining the change in income-related inequality in vision difficulty. CONCLUSION: Vision difficulty was more prevalent in low-income populations. Our study enhances the understanding of socioeconomic disparities in vision difficulty, which could inform how to best target the deployment of eye care resources to maximize the visual potential of the US population.

The Coaltion for Global Hepatitis Elimination's National Hepatitis Elimination Profiles assess the status of national data, policy, and programme development the elimination of viral hepatitis. Profiles from 33 countries and territories show progress, towards elimination of hepatitis B with 24 (73%) of them meeting the 2025 WHO interim target of 0·5% or less HBsAg prevalence in children younger than 5 years. 22 (67%) of countries and territories profiled have policies for universal hepatitis B birth-dose vaccination of newborns. Access to hepatitis B testing and treatment, including removing HBsAg screening and hepatitis B treatment patient co-payments and simplifying treatment algorithms, remains suboptimal, especially in low-income and middle-income countries and territories. Of the seven profiled countries and territories meeting the 60% WHO 2025 diagnosis coverage target, all but one (Rwanda) is a high-income country or territory. No country or territory has met the WHO 2025 treatment target of at least 50% of people living with hepatitis B receiving treatment. The profiles guide national planning and identify priorities for resource mobilisation to further accelerate hepatitis B elimination.

The Coalition for Global Hepatitis Elimination's National Hepatitis Elimination Profiles assess the status of national data, policy, and programme development for the elimination of viral hepatitis. To date, profiles from 33 countries and territories have been developed. These profiles reveal that 30 (91%) countries and territories have hepatitis C national action plans, 11 (33%) have systems to monitor hepatitis C-related mortality, 16 (48%) have systems to monitor hepatitis C incidence, and 18 (55%) have systems to track the number of people tested and treated. Some countries and territories continue to uphold barriers to hepatitis C treatment, with 12 (36%) still having partial or full restrictions on prescribing authority for non-specialists. Ten (30%) countries and territories have met the WHO 2025 diagnosis coverage target of 60%, five (15%) have met the treatment target of 50%, and seven (21%) have met the needle and syringe exchange target. Although there are examples of countries and territories across the income spectrum meeting these targets, policy development in low-income and middle-income countries and territories generally lags behind that in high-income countries and territories.

OBJECTIVES: To evaluate the effect of high-dose isoniazid in patients with isoniazid-resistant TB by its bactericidal activity after 1 or more weeks of treatment. SUBJECTS AND METHODS: Using the rapid direct method of phenotypic drug susceptibility testing, we screened persons with positive sputum microscopy results and genotypic drug resistance for isoniazid resistance. Those with no growth at a critical concentration of 2.0 mg/L were invited to participate in a trial of high-dose isoniazid monotherapy lasting 6 days. After 3 days of no treatment, patients received isoniazid 15 mg/kg and were followed with serial quantitative sputum cultures from Days 0 to 6. RESULTS: We enrolled 15 patients after a median of 2 weeks standard first-line treatment. Their median bacillary count on Day 0 was 4.9 log(10) cfu/mL on solid agar, and the time to detection (TTD) was 200 h in liquid medium. Neither metric showed meaningful change in bacillary burden over 6 days, declining by a non-significant 0.08 log(10) cfu/mL/d on solid media and slowing TTD by 23 h. These effects did not differ by degree of isoniazid resistance or specific Inhibin Subunit Alpha (inhA) gene mutations. CONCLUSIONS: The utility of high-dose isoniazid against low-level isoniazid resistance beyond the first 2 weeks of chemotherapy should be reconsidered.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among people living with HIV (PLHIV). Antiretroviral therapy (ART) initiation lowers the risk of HIV-associated TB. Earlier studies have shown TB incidence to be high in the first year of ART. We undertook a study to (1) assess the incidence of TB and (2) associated factors among persons initiating ART in a rural cohort. METHODS: We conducted a retrospective cohort analysis study among PLHIV aged ≥ 18 years, initiated on ART from January 1, 2012, to December 31, 2019, and TB disease-free at the time of ART initiation, at Kalisizo ART clinic. TB disease incidence was calculated by dividing the number of new TB cases by the total follow-up time expressed per 100 person-years among persons followed up until the date of incident TB disease, loss to follow-up, transfer out, death or censored at the end of the study; whichever occurred first. Factors associated with TB disease incidence were assessed in the multivariable analysis by Poisson regression analysis at 5% significance level. RESULTS: For the period 2012 to 2019, 2,589 PLHIV were initiated on ART; 57% (1,470/2,589) were female. Females were more likely to be aged below 35 years while males were more likely to be aged 25-44 years (p < 0.001). Eighty-seven per cent (1,269/1,470) of females compared to 78% (866/1,119) of males were in WHO clinical stage 1 (p < 0.001). Sixty-one TB disease events were observed in 7,363 person-years. The overall TB disease incidence was 0.83 (95% CI: 0.63-1.06) per 100 person-years. Males were more likely than females to develop TB disease, adjusted incidence rate ratio (adj IRR) 2.13 (95% CI: 1.27-3.57) per 100 person-years, p = 0.004. Compared to using ART for 0-5 months, time on ART was associated with a lower TB incidence rate at 6-12 months, 13-24 months, > 24 months (adj IRR 0.20 (95% CI: 0.09-0.46), 0.14 (95% CI: 0.06-0.33), 0.16 (95% CI: 0.08-0.31) p < 0.001 respectively). CONCLUSIONS AND RECOMMENDATIONS: Incidence of TB among PLHIV on ART was low in this rural population. Clinicians offering care to people with HIV in the rural setting should have a heightened index of suspicion for TB disease.

INTRODUCTION: Pakistan's acute flaccid paralysis (AFP) surveillance system is an essential part of efforts to eradicate poliomyelitis, as Pakistan and Afghanistan are the only countries where wild poliovirus remains endemic. The two primary performance indicators for AFP surveillance are the non-polio AFP rate for children aged <15 years and stool adequacy, defined as the percentage of AFP cases for which two timely stool samples arrive at the laboratory in good condition. Despite consistently meeting targets for both indicators at the national level, some districts in Pakistan failed to meet the stool adequacy target of ≥80% in 2023 or had declining stool adequacy. In March 2024, we assessed AFP surveillance in 12 districts in Pakistan with low stool adequacy to characterize barriers to meeting the target. METHODS: The assessment included review of case investigation forms from AFP cases with patient paralysis onset during January 2023-mid-March 2024 with inadequate stool samples, as well as visits to health facilities serving as active surveillance sites and interviews with surveillance and laboratory personnel. RESULTS: The most common barrier to stool adequacy was a delay between onset of paralysis and AFP case notification, which occurred in 111 of 158 (70%) inadequately sampled AFP cases reviewed. This delay was most frequently attributed to missed reporting by healthcare facilities, caretakers seeking healthcare many days after paralysis onset, or a combination of both. Additionally, only 63% of health facilities showed adequate active surveillance visit compliance. DISCUSSION: The assessment exposed gaps in AFP surveillance knowledge for some health facility staff, especially nurses and other paramedical or support professionals. Recommendations to improve the AFP surveillance system include monitoring and encouraging compliance with systematically scheduled health facility visits, increasing the frequency of AFP surveillance orientations, including paramedical professionals in AFP surveillance training, and developing a comprehensive messaging plan to increase knowledge about prompt reporting of AFP among healthcare providers and the public.

INTRODUCTION: Municipalities can improve access to food through transit planning. The primary objective of this study was to describe the prevalence of public transit supports for food access among a sample of US municipalities and their association with the municipalities' sociodemographic characteristics. METHODS: This study used a nationally representative sample (N = 1,956) of US municipalities with a population of at least 1,000 that responded to the 2021 National Survey of Community-Based Policy and Environmental Supports for Healthy Eating and Active Living. We assessed 4 outcomes: public transit availability and planning, presence of demand responsive transportation (DRT), DRT services to food retail destinations (farmers markets and supermarkets), and consideration of these locations in transit planning. We used χ(2) tests to compare the prevalence of outcomes by municipal characteristics and multivariable logistic regression to calculate odds ratios to assess the relationship between municipal characteristics and having DRT. RESULTS: Approximately half (weighted 53.2%) of municipalities reported having or planning for public transit, of which 27.1% and 52.6% reported considering service to farmers markets or supermarkets, respectively. Approximately one-third (35.5%) of municipalities reported having DRT, of which 52.0% and 84.4% reported services to farmers markets or supermarkets, respectively. All outcomes significantly differed by municipal characteristics. We found higher odds of having DRT in municipalities with 2,500 to 50,000 people or more (vs <2,500 people); those with 50% or less of the population being non-Hispanic White (vs >50% non-Hispanic White); and municipalities containing low-income/low-access tracts. The odds of having DRT were lower in rural (vs urban) municipalities and in those in Northeast and South (vs the Midwest). CONCLUSION: Results suggest opportunities for municipalities to use transit planning to improve food access, especially in northeastern, southern, smaller, or rural communities.

OBJECTIVES: To systematically review evidence on whether medications with smooth muscle relaxant properties improve patient and provider outcomes for intrauterine device (IUD) placement. STUDY DESIGN: We searched multiple databases through August 2022 for randomized clinical trials assessing smooth muscle relaxants for IUD placement. Primary outcomes were pain experienced with IUD placement, provider ease of placement, need for adjunctive placement measures, placement success, patient satisfaction with procedure, medication side effects occurring before clinic discharge, and adverse events occurring before clinic discharge. We extracted data from included articles, assessed risk of bias for each trial, narratively summarized results, and determined certainty of evidence for all outcomes. RESULTS: Five trials met inclusion criteria; four trials had low risk of bias and one had moderate risk. Two trials of topical nitroprusside gel or nitroglycerin ointment found no differences in patient pain, provider ease of placement, patient satisfaction, placement success, side effects, or adverse events. One trial suggested that drotaverine plus mefenamic acid reduced patient pain but did not improve placement success. Two trials suggested that isonicotinic acid hydrazide reduced patient pain, improved provider ease of placement and patient satisfaction, reduced need for analgesia and for cervical dilation (in one trial) and did not increase side effects; neither trial reported improved placement success. CONCLUSIONS: Evidence on smooth muscle relaxants for IUD placement remains sparse with inconsistent findings across specific medications. Certainty of evidence for all outcomes was low for topical nitroprusside gel and nitroglycerin ointment, very low for drotaverine plus mefenamic acid, and mostly high for isonicotinic acid hydrazide. IMPLICATIONS: Before IUD placement, healthcare providers can counsel patients on the potential for pain during placement and options for pain management. However, more evidence is needed on specific smooth muscle relaxants to determine their effectiveness as an intervention for IUD placement.

INTRODUCTION: People who inject drugs (PWID) in Zambia are an understudied population at high risk for HIV acquisition and transmission. We report here on the progress within the PWID communities of Livingstone, Lusaka, and Ndola, Zambia towards the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets. METHODS: A biobehavioral survey used respondent-driven sampling to survey 235 PWID in Livingstone, 349 in Lusaka, and 259 in Ndola in 2021-22. Questions on HIV and injection drug use were administered, and blood was collected for HIV, syphilis, Hepatitis B, and Hepatitis C testing. Weighted prevalence and 95% confidence intervals (CIs) were calculated using Gile's sequential sampling estimator. RESULTS: In Livingstone, Lusaka, and Ndola, HIV prevalence among PWID was 11.9% (95% CI: 7.3, 16.5), 7.3% (95% CI: 4.5, 10.2), and 21.9% (95% CI: 14.5, 29.3), respectively. Among HIV-positive PWID in Livingstone, 70.7% (95% CI: 55.4, 85.0) were aware of their HIV status (95% is 1st UNAIDS target), 100% of those were on antiretroviral therapy (ART) (95% is 2nd UNAIDS target), and 100% of those achieved viral load suppression (VLS) (95% is 3rd UNAIDS target). In Lusaka, 66.0% (95% CI: 49.3, 82.2) were aware, 75.7% (95% CI: 51.1, 99.9) were on ART, and 66.3% (95% CI: 42.1, 90.9) achieved VLS. In Ndola, 60.2% (95% CI: 44.1, 76.0), 100%, and 90.2% (95% CI: 82.2, 98.3) were aware, on ART, and achieved VLS, respectively. CONCLUSIONS: Awareness of HIV status was low among PWID living in Livingstone, Lusaka, and Ndola, Zambia. Treatment and VLS progress were lacking in Lusaka and Ndola as well with Lusaka showing the least progress toward all three UNAIDS targets. Our site-level findings highlight critical gaps in PWID-specific HIV awareness, treatment, and VLS status in three major urban areas in Zambia that limit progress toward HIV epidemic control in this hard-to-reach population.

New intervention methods and product formulations are needed to better control pyrethroid-resistant Aedes aegypti populations and mitigate the risk of mosquito-borne disease. ReMoa Tri is a novel adulticidal space spray that utilizes a different mode of action than the commonly used adulticides: pyrethroids and organophosphates. As a triple-action space spray, ReMoa Tri combines three components: Fenpropathrin, a mixed-type I/II pyrethroid; abamectin, a macrocyclic lactone; and C8910, a patented fatty acid chain. Prior studies performed by Collier Mosquito Control District showed that ReMoa Tri is effective at controlling type I pyrethroid-resistant Ae. aegypti mosquitoes. To further validate these results and the performance of ReMoa Tri, we conducted a semi-field evaluation using ground and aerial ULV (ultra-low volume) applications with field-caught deltamethrin-resistant Ae. aegypti and a susceptible Ae. aegypti laboratory strain. Ground evaluations tested ReMoa Tri and a type II pyrethroid-based product, DeltaGard. While ReMoa Tri was equally effective against Collier's deltamethrin-resistant Ae. aegypti and the susceptible laboratory strain, DeltaGard was effective against both strains, with reduced efficacy at farther distances. Similarly, aerial evaluations also showed that ReMoa Tri was equally effective against Collier's deltamethrin-resistant Ae. aegypti strain and susceptible laboratory strain. This study further confirms ReMoa Tri's potential as an effective alternative to pyrethroid-based adulticides, both in ground and aerial applications, for managing pyrethroid-resistant Ae. aegypti.

Background: Bacterial meningitis is a severe syndrome with dynamic epidemiology, but assessments of current trends are limited. We aimed to describe changing epidemiologic patterns among common bacterial causes of meningitis in the United States. Methods: We analyzed data on bacterial meningitis cases caused by Streptococcus pneumoniae, group B Streptococcus (GBS), Haemophilus influenzae, Neisseria meningitidis, and Listeria monocytogenes in 10 U.S. surveillance sites. We compared incidence (cases per 100,000) across four epidemiologic periods: 2008–2009, 2010–2019, 2020–2021, and 2022–2023. Findings: We identified 5,032 bacterial meningitis cases; among those with outcome data, 11% (573/5028) died. S. pneumoniae was the dominant pathogen (59% [2922/5032]) throughout. However, GBS predominated among infants aged 0–2 months (85% [660/775]), the age group with the highest incidence. Between 2008–2009 and 2010–2019, overall bacterial meningitis incidence declined from 1.3 to 1.1, driven by decreases in S. pneumoniae meningitis caused by serotypes contained in the 13-valent pneumococcal conjugate vaccine (PCV13) and N. meningitidis meningitis. Meningitis caused by non-b H. influenzae strains increased during this period. During 2020–2021, incidence declined to 0.7, driven by decreases in S. pneumoniae, H. influenzae, and N. meningitidis meningitis, regardless of organism subtype. During 2022–2023, incidence increased to 1.0, driven by increases in S. pneumoniae and H. influenzae meningitis. Case fatality ratios remained stable throughout. Interpretation: Bacterial meningitis incidence rates have declined since 2008, with a notable low during 2020–2021, followed by a resurgence during 2022–2023. Case fatality remains high. Strategies that provide effective and broader pneumococcal and H. influenzae serotype protection and prevent infant GBS meningitis could reduce residual meningitis burden. Funding: U.S. Centers for Disease Control and Prevention. © 2025

OBJECTIVES: To evaluate the potential contributions of routine opt-out testing (ROOT) in clinical settings and preexposure prophylaxis (PrEP) on achieving Ending the HIV Epidemic in the U.S. (EHE) incidence reduction goals in the South. DESIGN: Simulation Study. METHODS: An agent-based epidemic projection model simulated adherence to the CDC's ROOT guidelines. Simulations were informed by literature reviews, the National Survey of Family Growth and ARTnet. Interventions included ROOT in Community Health Center (CHC) and Emergency Departments (ED) alone and in combination. PrEP was modeled as either persistent at 2019 levels or expanding consistent with historical trends. RESULTS: ROOT in CHCs and EDs averted 13.9% (95%SI: -15.5, 42.4) of infections and increased the proportion of persons with HIV (PWH) who were aware of their status from 84.8% to 94.4% (95%SI: 92.8, 95.4). In conjunction with the ongoing expansion of PrEP the proportion diagnosed increased from 84.8% at baseline to 95.1% (95% SI: 93.9, 96.4) and 23.3% (95% SI: -7.9, 50.6) of infections were averted, reducing the annual incidence rate by 42.4% compared to the baseline scenario. CONCLUSIONS: In our analysis, ROOT coupled with the ongoing expansion of PrEP averted almost a quarter of new infections over the 8 years from 2022 to 2030. While short of the overall EHE goal of 90%, it represents substantial potential progress for a low-cost and low-barrier intervention. ROOT also provides a method for identifying PWH who are undiagnosed both in and out of priority populations, those out of care, and individuals reluctant to seek screening.

Introduction: Drowning is a major public health problem. There are about 4,500 fatal unintentional drownings in the United States each year, and more children ages 1–4 die from drowning than from any other cause. Some sociodemographic characteristics are associated with increased risk of unintentional fatal drowning. The purpose of this study was to better understand the association between county-level social vulnerability and unintentional fatal drowning. Methods: This study used the 2014 Centers for Disease Control and Prevention and Agency for Toxic Substances and Disease Registry's (CDC/ATSDR) Social Vulnerability Index (SVI) and mortality data from the National Vital Statistics System from 1999 to 2023. Counties were ranked and categorized into tertiles across social vulnerability scores for all indicators of the SVI. Negative binomial regression was used to estimate crude rate ratios (RR) and 95% confidence intervals comparing county-level fatal drowning rates and the SVI indicators. Results: County-level social vulnerability is associated with unintentional fatal drowning. Counties with high overall social vulnerability had fatal drowning rates 1.59 times as high as counties with low social vulnerability. These associations were most pronounced for the SVI indicators of socioeconomic status (RR = 1.56), disability status (RR = 1.49), and proportion of mobile homes (RR = 1.62). Conclusions: While the reasons for the associations between indicators of the SVI and higher rates of drowning are not fully understood, counties with high social vulnerability may be associated with reduced access to swimming pools, affordable swimming lessons, and other evidence-based drowning prevention strategies. Practical Applications: Communities can use the SVI and other indicators of risk to support drowning prevention program implementation, ensuring strategies reach and are tailored to populations most at risk of drowning. © 2025 National Safety Council and Elsevier Ltd

IMPORTANCE: Most of the 2.3 million annual neonatal deaths occur in sub-Saharan Africa and South Asia, with perinatal asphyxia and neonatal sepsis being the leading causes of neonatal mortality. Most neonatal deaths are considered preventable through high-quality clinical care, which includes adherence to clinical care guidelines. OBJECTIVE: To assess adherence to World Health Organization clinical care guidelines for management of perinatal asphyxia and neonatal sepsis and to identify patient-level factors in adherence among neonates who died from these conditions. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study obtained data from December 2015 through October 2023 from the Child Health and Mortality Prevention Surveillance (CHAMPS) catchment areas in 7 low- and middle-income countries in sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and South Asia (Bangladesh). Participants were neonates who were born alive and were aged 0 to 28 days at the time of death and had either perinatal asphyxia or neonatal sepsis. EXPOSURE: Medical records of neonates who died from perinatal asphyxia or neonatal sepsis determined by postmortem diagnostics. MAIN OUTCOMES AND MEASURES: The main outcome was the proportion of deceased neonates who received guideline-adherent treatments before they died. Mixed-effect multivariable logistic regression analyses were performed to identify factors associated with administration of at least bag-valve-mask (BVM) ventilation for perinatal asphyxia. RESULTS: Of the 1194 neonates (median [IQR] age at the time of death, 2 [1-6] days; 692 males [58.0%]) who died and were enrolled in CHAMPS with available clinical data, 476 (39.9%) died from perinatal asphyxia, 562 (47.0%) died from neonatal sepsis, and 156 (13.1%) from both conditions. These neonates had a median (IQR) birth weight of 2130 (1266-2988) g. For cases with perinatal asphyxia, guideline adherence ranged from 12.2% (n = 77) for adrenaline administration to 85.4% (540) for supplemental oxygen administration. Only 4.4% of neonates (28) with perinatal asphyxia received all recommended treatments. Among cases with neonatal sepsis, antibiotics were administered to 86.8% (623), although the recommended treatment was administered to only 61.0% (438). In multivariable analyses, neonates in whom clinicians accurately identified perinatal asphyxia were more likely to receive BVM ventilation than those who had received discordant antemortem and postmortem diagnoses (adjusted odds ratio, 2.00; 95% CI, 1.29-3.12). CONCLUSIONS AND RELEVANCE: In this cross-sectional study, clinical care guideline adherence was suboptimal among neonates who died from perinatal asphyxia or neonatal sepsis. This finding underscores the critical need to increase adherence in regions with high rates of neonatal mortality and may inform strategies for strengthening health systems to support compliance with clinical care guidelines.

BACKGROUND: We calculated prevalences of birth defects among infants of participants in the Centers for Disease Control and Prevention's (CDC) COVID-19 Vaccine Pregnancy Registry (C19VPR). METHODS: C19VPR enrolled women receiving COVID-19 vaccines ≤ 30 days before the last menstrual period or during pregnancy from December 2020 through June 2021. We included 19,931 participants with singleton pregnancies ending ≥ 20 weeks' gestation who did not report COVID-19 illness during pregnancy. Clinicians identified birth defects from participant-reported infant health information up to 4 months after birth. We compared C19VPR birth defect prevalences to published pre-pandemic estimates. For seven defects originating during embryogenesis (cleft lip with/without cleft palate, atrial septal defect, coarctation of the aorta, ventricular septal defect, esophageal atresia or stenosis, hypospadias, kidney agenesis/hypoplasia/dysplasia), we estimated prevalence ratios comparing those vaccinated < 14 weeks' to those vaccinated ≥ 14 weeks' gestation. RESULTS: Participants reported receiving Pfizer-BioNTech vaccines (59.0%), Moderna (38.2%), and Janssen (2.8%) vaccines. Most (65.2%) participants received their first COVID-19 vaccine after the first trimester. The prevalence of major birth defects was 3.8%. Among defects with comparator estimates available (n = 50), 35 were below or within expected ranges. C19VPR prevalences were higher than the comparator confidence interval for 15 defects; however, C19VPR confidence intervals included comparator estimates. Prevalences did not differ by the timing of vaccination for seven defects examined. CONCLUSIONS: Birth defects prevalence estimates among infants born to women receiving COVID-19 vaccines during or just prior to pregnancy were generally similar to pre-pandemic estimates. While there was no strong evidence of associations between vaccination and specific defects, statistical power was low.

Orofacial clefts (OFC) are a common birth defect with few known risk factors (e.g., smoking). Maternal diet is associated with birth defects, though the relationship with OFC is less clear as studies typically only investigate single nutrients. We assessed the association between periconceptional maternal diet and OFC in the United States, using the National Birth Defects Prevention Study (1997-2011), including 3,649 cases (2,480 cleft lip with/without palate [CL/P] and 1,169 cleft palate [CP]) and 10,584 controls (infants without a birth defect). Using latent class analysis, we derived dietary patterns based on relative consumption of self-reported food items via food frequency data. We used logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CIs) for the effect of dietary patterns on OFC. Four patterns were identified: Prudent (reference), Western, Low-Calorie Western, and Mexican. The Western diet had increased odds of CL/P (aOR: 1.3, CI: 1.2-1.5) and CP (aOR: 1.2, CI: 1.1-1.4). Low-Calorie Western (CL/P aOR: 1.2, CI: 1.0-1.4; CP aOR: 1.0, CI: 0.9-1.2) and Mexican diets (CL/P aOR: 1.1, CI: 0.9-1.3; CP aOR: 0.8, CI: 0.6-1.1) had a weaker or null association. Findings underscore the importance of further investigation into the effect of periconceptional diet on OFC occurrence.

BACKGROUND: High-grade Plasmodium falciparum resistance to sulfadoxine-pyrimethamine in east and southern Africa has prompted trials evaluating intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine as an alternative to sulfadoxine-pyrimethamine. We aimed to provide an updated and comprehensive review of trials conducted in areas of high P. falciparum resistance that compared the efficacy of two types of IPTp regimens on maternal, birth, and infant outcomes. METHODS: We conducted two-stage, individual participant data meta-analyses of randomised trials comparing IPTp with dihydroartemisinin-piperaquine to sulfadoxine-pyrimethamine on maternal, birth, and infant outcomes. We searched the WHO International Clinical Trials Registry Platform, ClinicalTrials.Gov, PubMed, and the Malaria in Pregnancy Consortium Library, on July 30, 2020 (updated on September 24, 2024), without restrictions by publication date, peer-review status, or language. Eligible trials enrolled HIV-uninfected pregnant women, followed participants to delivery, included participants with no prior IPTp use during the current pregnancy, and were conducted in areas with high-level parasite resistance to sulfadoxine-pyrimethamine (i.e., PfDHPS 540E ≥ 90% and/or 581G>0%). Only singleton pregnancies were analysed. The primary endpoint was a composite measure of any adverse pregnancy outcome defined as fetal or neonatal loss, small-for-gestational age, low birthweight, or preterm birth. Summary estimates were generated using a random-effects model. Gravidity subgroup analyses were performed. Causal mediation analyses were used to investigate the maternal mechanisms underlying the effect of IPTp regimens on birth outcomes. The meta-analysis is registered in PROSPERO (CRD42020196127). FINDINGS: Of 85 screened records, six trials (one multi-country trial) from Kenya, Malawi, Uganda and Tanzania contributed data on 6646 pregnancies. Compared to sulfadoxine-pyrimethamine, dihydroarteminsinin-piperaquine was associated with a 69% [95% CI: 45%-82%] lower incidence of clinical malaria during pregnancy, a 62% [37%-77%] lower risk of placental parasitaemia, and a 17% [0%-31%] lower incidence of moderate maternal anaemia. In contrast, sulfadoxine-pyrimethamine was associated with higher mean maternal weight gain (34 g/week [17-51]). There were no statistically significant differences in the composite adverse pregnancy outcome (RR = 1.05 [0.92-1.19]; I (2) = 48%). Individual components of the primary outcome showed no statistically significant differences in the risks of fetal loss (RR = 0.94 [0.61-1.46]), preterm birth (RR = 0.93 [0.76-1.14]), low birthweight (RR = 1.09 [0.83-1.43]), or neonatal loss (RR = 0.73 [0.42-1.26]), though findings may have been underpowered. Small-for-gestational-age risk was 15% (3%-24%) lower in the sulfadoxine-pyrimethamine arm, particularly among multigravidae (a 22% reduction vs 9% in primigravidae). Among multigravidae, infant stunting and underweight by two months was 20% [8%-30%] and 35% [17%-49%] lower in the sulfadoxine-pyrimethamine arm compared to dihydroartemisinin-piperaquine. Compared to dihydroartemisinin-piperaquine, sulfadoxine-pyrimethamine was associated with higher mean newborn birthweight (mean difference (MD) = 50 g [95% CI: 13-88]; p = 0.0090, I(2) = 61%) and BWGA z-scores (MD = 0.12 [95% CI: 0.05-0.20]; p = 0.0012, I(2) = 51%), but not gestational age at birth (MD = 0 weeks [95% CI: -0.11 to 0.12]; p = 0.94; I(2) = 42%). Infant wasting by two months was 13% [3%-22%] lower in the sulfadoxine-pyrimethamine arm, regardless of gravidity. Mediation analyses indicated that 15% [0%-19%] of sulfadoxine-pyrimethamine's superior effect on small-for-gestational-age risk was mediated by its greater impact on gestational weight gain. INTERPRETATION: In areas with high P. falciparum sulfadoxine-pyrimethamine resistance, dihydroartemisinin-piperaquine offers superior antimalarial efficacy than sulfadoxine-pyrimethamine. However, replacing sulfadoxine-pyrimethamine with dihydroartemisinin-piperaquine alone may not lead to improved maternal and infant health outcomes. Instead, it could result in slightly reduced gestational weight gain and a modest increase in the risk of small-for-gestational age births, and poor infant growth by two months of age. Future research evaluating alternative strategies for IPTp are needed. FUNDING: This work was supported by the Bill and Melinda Gates Foundation and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

There is limited population-level data on the pre-exposure prophylaxis (PrEP) care continuum in eastern Africa. Here, we assessed the PrEP care continuum following PrEP rollout in a Ugandan community with ~40% HIV seroprevalence. We used cross-sectional population-based data collected between September 3 and December 19, 2018 from a Lake Victoria fishing community in southern Uganda to measure levels of self-reported PrEP awareness, ever-use, and discontinuation following 2017 PrEP rollout via a U.S. President's Emergency Plan for AIDS Relief (PEPFAR)-supported phased implementation program. Our analysis included HIV-seronegative persons reporting having ever received an HIV test result. We examined associations between demographic, behavioral, and health utilization factors with each outcome using age-adjusted modified Poisson regression. There were 1,401 HIV-seronegative participants, of whom 1,363 (97.3%) reported ever receiving an HIV test result. Median age was 29 years (IQR: 23-36), and 42.3% (n = 577) were women. Most (85.5%; n = 1,166/1363) participants reported PrEP awareness, but few (14.5%; n = 197/1363) reported ever using PrEP. Among 47.7% (375/786) of men and 29.3% (169/577) of women PrEP-eligible at time of survey, 18.9% (n = 71/375) and 27.8% (n = 47/169) reported ever using PrEP, respectively. Over half (52.3%, n = 103/197) of those who had ever used PrEP, self-reported current use. In this Lake Victoria fishing community, there were low levels of PrEP use despite high levels of PrEP awareness and eligibility, particularly among men. Efforts that enhance awareness of HIV risk and increase PrEP accessibility may help increase PrEP use among HIV-seronegative persons in African settings with high HIV burden.

Healthcare workers and patients are at continual risk for healthcare-associated infections due to poor hand hygiene. Programs that support appropriate hand hygiene practices may mitigate this risk, although implementation is challenged by several barriers, including limited availability of hand hygiene products at the point of care, as described by the world health organization (WHO). In this study, we used mixed methodologies, including in-depth interviews and surveys to assess the knowledge, attitudes, practices, and barriers to appropriate hand hygiene practices among healthcare workers from 19 public primary and secondary healthcare facilities in Quetzaltenango, Guatemala. The qualitative data analyzed by thematic axes and quantitative data are described. We found that healthcare workers have a strong understanding of the importance of hand hygiene and how it contributes to patient health. We encountered knowledge gaps about the route of transmission of pathogens and how to prevent spread. Nevertheless, healthcare workers acknowledged the importance of training programs to strengthen hand hygiene practices. Potential barriers to improving hand hygiene practices included a lack of adequate infrastructure and resources for practicing hand hygiene with alcohol hand sanitizer, soap, and water. The results of this evaluation provide useful information for supporting hand hygiene practices in participant healthcare facilities and contributes to efforts to reduce the risks of healthcare-associated infections. Our findings likely apply to local healthcare facilities in other low- and middle-income countries and may be used to design hand hygiene educational materials for healthcare workers.

With the development of new vaccine technologies, such as mRNA vaccines, tissue studies are becoming increasingly important. Knowledge of the antigen expression amounts and where the antigen accumulates in the body is essential for designing safe and effective vaccines. Mammalian tissues present challenges in the detection and accurate quantification of target proteins because of their complexity and the lack of protocols that efficiently extract proteins with minimal sample loss. Here, we describe a protocol for the detection and accurate quantification of protein targets in commercially available snap-frozen lung, liver, kidney, and spleen of European domestic ferrets (Mustela putorius furo) by isotope dilution mass spectrometry (IDMS). Housekeeping proteins were chosen that range in abundance to account for different masses of tissue slices of the same organ. Target peptides used for IDMS quantification were conserved across several of the common animal model systems, including baby hamster kidney, mouse, and ferret. Hemagglutinin, the primary antigen of an influenza vaccine, was added at various concentrations to demonstrate the recovery of low-abundance proteins from the complex tissue homogenate. By using housekeeping proteins and a preparation protocol that minimizes sample loss, this study shows that IDMS can accurately quantify proteins in mammalian tissues with unmatched sensitivity and specificity.

Control of endemic infectious diseases is often impeded by the lack of sensitive and specific yet easy-to-obtain biomarkers. Antibody fragment crystallizable (Fc) regions, such as Fc glycosylation, which are modulated in a pathogen-specific and disease-state-specific manner have emerged as potential such biomarkers. However current methods to perform large-scale antigen-specific antibody Fc feature screening for biomarker discovery often require too much sample volume, cost and expertise to be realistically realizable in many disease contexts. Here we present a simple, flexible and reconfigurable microfluidic device, made using rapid prototyping techniques, that can perform highly multiplexed and high-throughput biomarker discovery targeting both antibody fragment antigen-binding (Fab) and Fc features including antigen specificity, antibody isotypes, subclasses, N-glycosylation and Fc receptor binding. Using integration of an antigen microarray and reconfigurable microfluidics for sample and probe distribution, the device can perform a total of 1400 assays measuring 100 antibody Fab and Fc features per sample from a low sample volume (15 μL). The device demonstrates cleanroom-free simple fabrication and ease of use comparable to standard immunoassay platforms. Performance comparable to existing methods was validated and a biomarker screening for schistosomiasis, a helminth-mediated infection, was performed using clinical samples where antibody subclass-based biomarkers were successfully identified distinguishing current infection from former infection and endemic controls.

OBJECTIVES: Thrombophilia is associated with an elevated risk of thrombosis, which may be further elevated with use of hormonal contraception. Our objective was to update a previously published systematic review on thrombosis risk with use of hormonal contraception among women with thrombophilia. STUDY DESIGN: We conducted a systematic review of five databases from database inception through December 8, 2022. We searched for articles that examined risk of venous thromboembolism (VTE) or arterial thromboembolism (ATE) in women with thrombophilia using hormonal contraception compared with women using non-hormonal or no contraception. We assessed risk of bias for each study and certainty of evidence for all outcomes. RESULTS: Eighteen articles met inclusion criteria; four had moderate risk of bias and 14 had high risk of bias. Odds of VTE in women with factor V Leiden (FVL) mutation or prothrombin (PT) gene mutation were elevated in combined oral contraception (COC) users vs non-users. Odds of VTE were elevated in COC users with FVL mutation, PT gene mutation, both FVL and PT mutations, antithrombin (AT) deficiency, or protein C deficiency compared with non-users without the mutation. Odds of stroke were elevated in COC users with FVL mutation compared with non-users without the mutation. Evidence was mixed on whether risk was elevated in women with protein S deficiency using COC compared with non-use. One study found elevated odds of VTE in women with FVL mutation but not women with PT gene mutation using progestin-only contraception (POC), compared with non-users without the mutation. CONCLUSIONS: Overall, studies found elevated odds of VTE and ATE in women with thrombophilia using COC compared with non-users without thrombophilia. The certainty of evidence for all outcomes is low. Evidence is also limited by small numbers of women and minimal evidence on use of patch, ring, or POC, and is insufficient to assess differential risk by all thrombophilia types. IMPLICATIONS: Use of estrogen-containing hormonal contraception might further elevate risk of thrombosis among women with thrombophilia. Further study is needed on safety of POC use in women with thrombophilia.

Bacterial meningitis is a significant public health concern, with over 1.2 million cases reported globally each year. Rwanda is at increased risk of meningitis outbreaks due to its proximity to countries that lie in the meningitis belt. Rwanda has been conducting surveillance and recording meningitis outbreak cases across the country since 2012. We evaluated the meningitis surveillance system at Kibogora Level Two Teaching hospital, Nyamasheke district of Rwanda to assess whether the surveillance objectives were being met. The study was cross-sectional, using purposive sampling to select healthcare providers participating in the meningitis surveillance. Rwanda's bacterial meningitis data from 2017 to 2021 was collected from clinical registers and Rwanda's electronic integrated disease surveillance system (eIDSR) from Kibogora Level Two Teaching Hospital catchment area, Nyamasheke district, Rwanda. The study area was chosen because a meningitis outbreak was recorded in the area and its bordering country namely Democratic of Republic of Congo (DRC) prior to the current study period. Information on the participant's demographics, occupation, training, professional experience, and their perception on the surveillance system were gathered using a structured questionnaire. Meningitis surveillance systems attributes including usefulness, acceptability, and flexibility were assessed and categorized as poor (< 50% score), reasonable (50-69%), good (70-90%), or excellent (> 90%) in reference to the study conducted on the evaluation of the meningitis surveillance system in Luanda Province, Angola in March 2017. Data collected from clinical registers and eIDSR were used to assess core functions of the meningitis surveillance system including accuracy in detection of cases, laboratory confirmation of cases, and availability of evaluation reports. Descriptive statistics were analyzed using Microsoft Office Excel. Thirty-one healthcare providers working on meningitis surveillance in the Kibogora Level Two Teaching Hospital were interviewed. During the period under evaluation, 48 suspected cases of meningitis were identified; 43 (90%) met the surveillance case definition, and only 10 (21%) were reported to eIDSR (completeness). Attributes such as flexibility scored good while stability and acceptability scored reasonable. Out of 48 suspected meningitis cases, only 2 (4%) samples were collected from patients and sent to the hospital laboratory for analysis. This study found a good knowledge level of the meningitis surveillance system among healthcare workers; however, the system's core functions, such as notification rate and laboratory confirmation were found to have gaps. The notification rate could be improved by conducting regular refresher courses for healthcare workers supporting surveillance system. Moreover, MoH could enhance the implementation of a national policy requiring mandatory CSF sample testing to confirm pathogens for all suspected cases. Future studies should explore performance-based incentives to improve reporting completeness. Rwanda's experience could provide insights for other low-resource settings facing similar surveillance challenges.

HIV prevention efforts have traditionally focused on urban areas, yet about one-fourth of new HIV diagnoses in the U.S. are in non-urban areas. This study explored rural and urban differences in perceived HIV risk; perceived HIV stigma; and pre-exposure prophylaxis (PrEP) awareness, attitudes, beliefs, communication behaviors, and use to inform the development of communication messages to promote informed decision-making among available HIV prevention options, including PrEP. We conducted interviews, preceded by a brief survey, with 255 adults in 5 rural and 6 urban locations throughout the U.S. with high HIV burden. Participants from rural areas more frequently described their risk of getting HIV as low compared with those from urban areas, although partly due to differences in gender/sexual identity and sexual risk. Participants from rural areas more frequently reported perceived stigma around getting tested for HIV, taking PrEP to prevent HIV, or having HIV and less frequently reported having heard of PrEP and having a healthcare provider talk with them about PrEP compared with those from urban areas. No participants from rural areas reported using PrEP, although 48% of those with HIV-negative or unknown status were at substantial risk based on reported risk factors. Our findings highlight notable differences in perceived HIV risk; perceived HIV stigma; and PrEP awareness, attitudes, beliefs, communication behaviors, and use between individuals residing in rural and urban areas, suggesting that HIV prevention messaging needs to be tailored for rural audiences to support receptivity.

Understanding disparities in salmonellosis burden is critical for developing effective, equitable prevention programs. Past efforts to characterize disparities were limited in scope and by the analytical methods available when the study was conducted. We aim to address this gap by identifying disparities in salmonellosis incidence between counties with different determinants of health (DOH) profiles. Using national U.S. Laboratory-based Enteric Disease Surveillance (LEDS) data for 1997-2019, age-adjusted county-level salmonellosis incidence/100,000 persons was calculated and linked to publicly available DOH data. We used hurdle counterfactual random forest (CFRF) to quantify, for each DOH, the risk that (i) ≥1 versus no cases were reported by a county, and (ii) when ≥1 case was reported, whether a high (≥16 cases/100,000 persons) or low incidence (≥1 & <4 cases/100,000 persons) was reported. Risk in both models was significantly associated with demographic DOH, suggesting a disparity between counties with different demographic profiles. Risk was also significantly associated with food, healthcare, physical, and socioeconomic environment. The risk was generally greater for counties with more negative food resources, and for under-resourced counties (e.g., fewer healthcare and social services, fewer grocery stores). Risk was also significantly higher if any extreme weather event occurred. The study also found that underreporting and underascertainment appeared to result in underestimation of salmonellosis incidence in economically marginalized and under-resourced communities. Overall, our analyses indicated that, regardless of other county characteristics, extreme weather was associated with increased salmonellosis incidence, and that certain communities were differentially disadvantaged toward a higher incidence. This information can facilitate the development of community-specific prevention efforts.

SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity. However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. Here we combine daily longitudinal sampling of individuals with replicate sequencing to increase the accuracy of and lower the threshold for variant calling. We sequenced 577 specimens from 105 individuals in a household cohort during the BA.1/BA.2 variant period. Individuals exhibited extremely low viral diversity, and we estimated a low within-host evolutionary rate. Within-host dynamics were dominated by genetic drift and purifying selection. Positive selection was rare but highly concentrated in spike. A Wright Fisher Approximate Bayesian Computational model identified positive selection at 14 loci with 7 in spike, including S:448 and S:339. This detectable immune-mediated selection is unusual in acute respiratory infections and may be caused by the relatively narrow antibody repertoire in individuals during the early Omicron phase of the SARS-CoV-2 pandemic.

Objectives. HIV preexposure prophylaxis (PrEP) use has increased since its US Food and Drug Administration approval in 2012. Our objective was to describe trends in PrEP use by US women. Methods. Using national pharmacy and HIV surveillance data, we calculated the PrEP-to-diagnosis ratio (PDR), a measure of PrEP prescriptions each year compared with HIV diagnoses the previous year, for women from 2017 to 2023. We also calculated PDRs in 2023 for the 20 counties with the highest numbers of diagnosed HIV infections among women and reviewed reports of public health activities conducted by recipients of Centers for Disease Control and Prevention HIV prevention funding. Results. The PDR for women was 1.5 in 2017, and it increased to 5.8 by 2023. In the 20 counties with the highest number of diagnosed HIV infections among women, PDRs ranged from 2.2 to 16.9. Counties with the highest PDRs conducted PrEP activities designed for women. Conclusions. PrEP is a highly effective HIV prevention intervention that can empower women to protect their health, but its use has been low. Public health and clinical interventions designed for women can increase their PrEP use and support ending the US HIV epidemic. (Am J Public Health. Published online ahead of print April 24, 2025:e1-e4. https://doi.org/10.2105/AJPH.2025.308056).

Young Black and Latino men who have sex with men are disproportionately affected by the U.S. HIV Epidemic, yet pre-exposure prophylaxis (PrEP) uptake remains low. To understand barriers and facilitators to PrEP uptake and persistence, we used a concurrent mixed methods design (quantitative: online surveys, n = 19; qualitative: individual interviews, n = 15) from providers (e.g., nurse practitioners, clinicians, and social workers) at 4 clinics providing PrEP services in Birmingham, Alabama and New York City. Although all providers were comfortable prescribing daily oral PrEP, they had concerns about on-demand PrEP (e.g., complex dosing schedule) and injectable PrEP (e.g., insurance barriers). Provider training is needed to address barriers to providing PrEP modalities beyond daily oral PrEP and increase uptake among young Black and Latino men who have sex with men. Additionally, in order to increase uptake of injectable PrEP, rising PrEP costs due to changes in the 340B Drug Pricing Program will need to be addressed.

A multistate measles outbreak, predominantly affecting members of close-knit communities with low measles vaccination coverage in New Mexico, Oklahoma, and Texas began in January 2025. As of April 17, a total of 800 cases have been reported in the United States in 2025; 654 (82%) cases in New Mexico, Oklahoma, and Texas have been associated with the ongoing outbreak. These cases represent an approximately 180% increase over the 285 measles cases reported in the United States during all of 2024, and the second highest annual case count in the United States in 25 years. Overall, 771 (96%) patients have been unvaccinated or had unknown vaccination status (77% were unvaccinated, and 14% had unknown vaccination status when excluding 590 cases reported by Texas, which requires explicit consent by law [i.e., opt-in] to enroll in the Texas Immunization Registry), 85 (11%) patients have been hospitalized, and three patients have died. Among 48 (6%) internationally imported cases, 44 (92%) occurred among U.S. residents. Endemic measles was declared eliminated in the United States in 2000 as a direct result of high 2-dose childhood coverage with the measles, mumps, and rubella (MMR) vaccine. However, measles cases and outbreaks continue to occur when travelers with measles return to the United States while they are infectious; larger U.S. outbreaks typically follow importation into close-knit communities with low vaccination coverage. Nationally, risk for widespread measles transmission remains low because of high population-level immunity. To prepare for and prevent measles cases and outbreaks, public health departments should continue working with trusted community messengers on culturally competent community engagement, education, vaccination efforts, and other community infection prevention approaches (e.g., case isolation, contact monitoring, and post-exposure prophylaxis) and coordinating with health care facilities and schools. Increasing national and local MMR vaccination coverage is essential to preventing measles cases and outbreaks.